Stereo-Selective Total Synthesis of Calofolic Acid – A: Vasorelaxant Natural Product

Abstract

Natural products are the molecules of nature; that is, they are molecules produced by living organisms. These molecules are synthesised by living organisms using the natural biosynthetic pathways. The total synthesis of such molecules using organic reactions has been a challenge since the 1900s. Calofolic Acids A-F are a class of natural products extracted from the bark of Calophyllum scriblitifolium. These compounds are shown to have vasorelaxation activity on phenylephrine-precontracted rat aortic rings. Through experiments, the possible mechanism of activity of calofolic acid A was proposed. Calofolic acid A inhibits the PI3K – AKT – PDE pathway in the VSMCs. This leads to the activation of the cAMP – PKA – MYPT1 – MLC pathway as well as the cAMP – PKA – MYPT1 – HSP 20 pathway. The overall effect of this is the vasorelaxation in the smooth muscle cells in the rat aorta. Herein, the efforts towards the total synthesis of the vasorelaxant natural product calofolic acid – A are described. Two different routes with different strategies are explored. The first route involved the synthesis of the chromanone core via alkene reduction which had some problems associated with it. However, the second route using a previously described work was successful and the total synthesis is nearing its conclusion.